amfAR Awards Give Boost to Promising Young HIV/AIDS Researchers

Latest round of Mathilde Krim Fellowships continuestradition of identifying and nurturing new talent

NEW YORK, Nov. 21, 2013—amfAR, The Foundation for AIDS Research, on Thursday announced the 2013 recipients of the Mathilde Krim Fellowships in Basic Biomedical Research. Named in honor of amfAR Founding Chairman Dr. Mathilde Krim, the Krim Fellowship program is an annual research initiative created to support bright young scientists seeking innovative solutions to HIV/AIDS.

“amfAR has always been a catalyst for groundbreaking studies that have the potential to transform HIV/AIDS research, and the Krim Fellowship program enables a new generation of researchers to make critical discoveries that advance our knowledge of the disease,” said amfAR CEO Kevin Robert Frost.

The six fellowship recipients—Rafael Cubas, Ph.D., of Vaccine and Gene Therapy Institute Florida, Port St. Lucie, FL; Dario Dilernia, Ph.D., of Emory University, Atlanta; Nuria Izquierdo-Userios, Ph.D., of AIDS Research Institute IrsiCaixa, Badalona, Spain; Kashif Sadiq, Ph.D., of Universitat Pompeu Fabra, Barcelona, Spain; Damien Tully, Ph.D., of Massachusetts General Hospital, Cambridge, MA; and Angela Wahl, Ph.D., of University of North Carolina at Chapel Hill—will each be awarded $150,000 over two years.

Dr. Tully will use his amfAR funding to study tissue from mouse models and recently infected people to better understand how the virus spreads once infection occurs. HIV is usually transmitted through mucosal membranes, such as at the vagina or rectum, but eventually the virus wreaks its havoc in the intestines. Dr. Tully will work with his mentor Dr. Todd Allen to understand the virus’ spread and evolution in the body that will yield vital information for the development of a vaccine and possibly a cure.

In an effort to determine which antibodies are best for building an effective HIV vaccine, Dr. Cubas will study a group of immune cells known as memory T follicular helper cells (Tfh) in HIV-positive individuals. In particular, Dr. Cubas plans to compare memory Tfh function to the the ability to produce broadly neutralizing antibodies in slow progressors, or HIV-positive people whose immune systems are better at keeping the virus in check than most.

Dr. Angela Wahl plans to better understand how HIV is transmitted through breast milk. The use of antiretroviral drugs to prevent mother-to-child transmission (MTCT) of HIV has virtually eliminated this mode of transmission in many parts of the world. However, how HIV is transmitted through breast milk is still not fully understood Dr. Wahl plans to study this and understand why breast milk inhibits HIV in the test tube but not when women breastfeed, with the goal ultimately of reducing the transmission of HIV to an infant from women who do not have access to antiretroviral therapy.

“We are confident that this group of talented scientists will unlock many findings that have the potential to benefit all people living with HIV, and we look forward to seeing how their studies progress,” said amfAR Vice President and Director of Research Dr. Rowena Johnston.

Dr. Krim has been a leading advocate of increased support for AIDS research since the early days of the epidemic. The first fellowships in her name were awarded in January 2008. Since then, amfAR has committed $5.2 million to support the development of outstanding young researchers who have demonstrated a commitment to preventing, treating and curing HIV/AIDS.

The following projects will be supported in the seventh round of Mathilde Krim Fellowships:

Rafael Cubas, Ph.D.; Mentor: Elias Haddad, Ph.D. Vaccine and Gene Therapy Institute Florida, Port St. Lucie, FL$149,886 (#108671)Memory Tfh cell function correlates with bNab generation during HIV infection: Most scientists believe that the ability of a vaccine to generate broadly neutralizing antibodies (bNab) will be critical to its ability to prevent HIV infection. In order to determine which antibodies are best, and to determine a way scientists can predict which infected people will generate the most effective antibodies, Dr. Cubas plans to study a subset of immune cells called memory T follicular helper cells. He will compare signs of the presence and activity of these cells in the blood to the ability to produce broadly neutralizing antibodies, in people identified as slow progressors. The immune systems of such people are believed to be better than usual at keeping the virus in check.

Dario Dilernia, Ph.D.; Mentor: Eric Hunter, Ph.D. Emory University, Atlanta, GA$150,000 (#108672)Identification of transmitted viral determinants of HIV pathogenesis: During HIV infection, the virus and immune system engage in an ongoing battle to gain ascendancy. When the immune system fights the virus, the virus mutates to evade the immune system, and vice versa. When the virus is transmitted to a new person, it usually encounters an immune system quite different from that of the transmitter. However, Dr. Dilernia has identified a population in Argentina whose immune systems do not greatly differ, and among whom a limited number of HIV strains have been transmitted. This situation will allow Dr. Dilernia to parse the role of the immune system in forcing the virus to make mutations that may result in a less fit virus, even when it is transmitted to a new person, shedding greater light on the process by which HIV causes disease.

Nuria Izquierdo-Useros, Ph.D.; Mentor: Javier Martinez-Picado, Ph.D. AIDS Research Institute IrsiCaixa, Badalona, Spain$150,000 (#108676)
Targeting engineered nanoliposomes for therapeutic purge of HIV-1 reservoirs:
Dr. Izquierdo-Useros seeks to utilize the properties of a type of immune cell known as the mature dendritic cell (mDC) to do two things: activate T cells latently infected with HIV, so that the virus they harbor is now susceptible to drug and immune attack; and boost their ability to cooperate with CD8+ killer T cells to target HIV. He will use ultra-tiny particles of lipid, known as nanoliposomes, to deliver these packages to the mDC. This strategy aims to attack reservoirs of latent HIV.

Kashif Sadiq, Ph.D.; Mentor: Andreas Meyerhans, Ph.D. Universitat Pompeu Fabra, Barcelona, Spain$150,000 (#108680)Enhanced premature self-activation of HIV-1 protease to induce apoptosis:
Dr. Sadiq recently built a model for the activation of the HIV protease enzyme, a critical target of anti-HIV drugs. When this occurs prematurely inside a cell, the cell and virus is killed. He plans to design potential drugs with the ability to induce this process as part of a “shock and kill” strategy for HIV.

Damien Tully, Ph.D.; Mentor: Todd Allen, Ph.D.Massachusetts General Hospital, Cambridge, MA$150,000 (# 108683)Getting to the guts of mucosal HIV-1 transmission through virus evolution: The great majority of new HIV infections occur by transmission through mucosal membranes, such as at the vagina or rectum, and a vaccine must be able to prevent transmission through such membranes. Regardless of the route of transmission, the majority of virus, and the damage it inflicts on cells, occurs in the lymphoid tissue in the intestines. In order to understand the initial events that lead to massive replication and destruction in the intestines, Dr. Tully proposes to use biopsy tissue from people who were very recently infected, as well as a mouse model, to understand how the virus spreads and the influence of the immune system’s attempts to quell the infection on the development of mutations. These studies will yield information important for the development of a vaccine and possibly a cure.

Angela Wahl, Ph.D.; Mentor: J. Victor Garcia-Martinez, Ph.D. The University of North Carolina at Chapel Hill, Chapel Hill, NC$150,000 (#108684)Mechanisms of oral HIV transmission in breast milk: Breast milk is a major route through which infants become infected with HIV, accounting for about half of all cases. The risk of transmission must be weighed against the benefits of breast milk in preventing severe health threats and death. The ability of HIV to transmit through breast milk is not fully understood and is somewhat surprising, given that the milk inhibits HIV in the test tube. Dr. Wahl plans to understand better the ability of breast milk to inhibit HIV in the test tube with the goal ultimately of reducing the transmission of HIV to an infant from women who do not have access to antiretroviral therapy.

About amfAR
amfAR, The Foundation for AIDS Research, is one of the world’s leading nonprofit organizations dedicated to the support of AIDS research, HIV prevention, treatment education, and the advocacy of sound AIDS-related public policy. Since 1985, amfAR has invested more than $366 million in its programs and has awarded grants to more than 2,000 research teams worldwide. For more information, please visit www.amfar.org.